Since the beginning of the AIDS epidemic, more than 24,000 cases have been reported to the CDC. The number of cases of AIDS, ARC and seropositive asymptomatic individuals is on a constant rise. The rapid spread of AIDS in the United States, Africa, Europe, South America and part of Asia points to the fact that we are faced with a major health problem at a pandemic level. The overall objectives of the proposed study are to investigate the presence of a protected immune reactivity to human immune deficiency virus (HIV) and to determine whether a less pathogenic form of HIV can be isolated from patients who have less aggressive forms of AIDS, namely long-term survivors (LTS) with Kaposi's sarcoma-AIDs (KS-AIDS). Specific aims include: 1) identification of LTS among KS-AIDS cases; 2) determination of the types, sequence of development, titers and specificity of various anti-HIV antibodies and their significance in a small, well- defined population of KS-AIDS and appropriate controls; 3) determination of cell mediated immune (CMI) reactivity toward HIV, the significance of this CMI reactivity in the course of the infection and the type or group specificity of the reaction; and 4) isolation of a possibly less pathogenic HIV variant from patients with less aggressive forms of AIDS. A battery of assays, including immunofluorescence, ELISA, Western blot, radioimmune precipitation and neutralizing assays, will be used for the detection of anti-HIV antibodies. CMI reactivity will be tested by measuring the lymphocyte proliferative responses to viral antigens. Conventional method will be used for isolation of HIV from selected cases. The proposed study will allow determination of the presence of a protective immunity toward HIV and the existence of a possibly less pathogenic form of this virus. This information is crucial in better defining the natural course of HIV infection and undoubtedly will be valuable to the development of appropriate vaccine and possibly a more effective mode of therapy.